PB2655: EVALUATION OF THE EFFICACY AND SAFETY IMMUNOSUPPRESSIVE THERAPY IN PATIENTS WITH ACQUIRED FACTOR VIII AND IX INHIBITOR
Authors: Derya Koyun, Güldane Cengiz Seval, Sinem Civrizbozdağ, Muhit Özcan, Pervin Topçuoğlu
Journal: HemaSphere (2023)

Topic: 33. Bleeding disorders (congenital and acquired) Background: Acquired factor inhibitor is a rare disorder and can cause life-threatening bleeding. Aims: Consequently, we report the efficacy and safety of our patients with acquired factor inhibitor treated with immunosuppressive drugs. Methods: We retrospectively investigated acquired factor inhibitor patients who were followed and treated in our center between November 2018 and March 2022. Bethesda assay was used to quantify factor inhibitors. The cut-off for positivity was set at 0.6 BU/mL and high inhibitor titers were defined as titers of >5 BU. The endpoint of study was the response of inhibitor eradication, duration of response, toxicity and bleeding control. Complete remission (CR) was defined as normal factor activity (70-140%) and undetectable factor inhibitor titer levels, and partial remission (PR) as restored factor coagulant activity that is >30%, reduction of factor inhibitor titer levels to <5 BU. Results: A total of seven patients, four of whom were male, with a median age of 65 (43-76) were included. Patients (pts)’ characteristics showed in Table 1. Acquired factor inhibitor was associated with malignancy (n=3), advanced age (n=2), postpartum period (n=1) and lupus anticoagulant (n=1). Median follow-up time was 9 months (range, 2-46) and the median OS was 27.5 mos (95% CI 11.8-43). High inhibitor titres were detected in four patients [median: 7.06 BU/ml (range, 5.76-100)] with negative antinuclear antibody (ANA), anti-cardiolipin IgG, lupus anticoagulant tests and all patients were treated with immunosuppressive drugs [bonn-malmö protocol (pts no:1), rituximab (pts no:1), metilprednisone in combination with cyclophosphamide (pts no: 2,3,4)]. The ORR was 100% (n=4) with 50% CR and 50% PR and one patient who developed the inhibitor in the postpartum period responded to single agent rituximab (Figure 1). The median time to response was 1.5 mos (range, 1-6). Immunosuppressive therapies were well tolerated, with no drug-related toxicity or infusion reactions. To achieve the hemostatic target, recombinant activated clotting factor VII (rFVIIa) and activated prothrombin complex concentrate (aPCC) were used in two out of four patients with active bleeding. Hemostasis was achieved successfully. Three patients developed a low-titre factor inhibitor and immunosuppressive drugs were not started for inhibitor elimination. Coagulation assays disappeared when the underlying condition was self-limited. Summary/Conclusion: Clinical presentation of factor inhibitors is highly variable and optimal treatment is not clearly established. Rituximab might be a promising treatment for therapy-resistant factor inhibitor and bleeding control was achieved with rFVIIa and aPCC. Treatment plan of patients with low-titre factor inhibitor should be provided considering the clinical situation and underlying disease.Keywords: Factor IX, Immunosuppressive therapy, Inhibitor, Factor VIII